Applying two approaches to detect unmeasured confounding due to time-varying variables in a self-controlled risk interval design evaluating COVID-19 vaccine safety signals, using myocarditis as a case example.

We test the robustness of the self-controlled risk interval (SCRI) design in a setting where time between doses may introduce time-varying confounding, using both negative control outcomes (NCOs) and quantitative bias analysis (QBA). All vaccinated cases identified from 5 European databases between 1 September 2020 and end of data availability were included. Exposures were doses 1-3 of the Pfizer, Moderna, AstraZeneca, and Janssen COVID-19 vaccines; outcomes were myocarditis and otitis externa (NCO). The SCRI used a 60-day control window and dose-specific 28-day risk windows, stratified by vaccine brand and adjusted for calendar time. The QBA included two scenarios: (i) baseline probability of the confounder was higher in the control window and (ii) vice versa. The NCO was not associated with any of the COVID-19 vaccine types or doses except Moderna dose 1 (IRR = 1.09, 95%CI 1.01-1.09). The QBA suggested even the strongest literature-reported confounder (COVID-19; RRmyocarditis = 18.3) could only explain away part of the observed effect from IRR = 3 to IRR = 1.40. The SCRI seems robust to unmeasured confounding in the COVID-19 setting, although a strong unmeasured confounder could bias the observed effect upward. Replication of our findings for other safety signals would strengthen this conclusion.

Describing diversity of real world data sources in pharmacoepidemiologic studies: The DIVERSE scoping review.

PURPOSE: Real-world evidence (RWE) is increasingly used for medical regulatory decisions, yet concerns persist regarding its reproducibility and hence validity. This study addresses reproducibility challenges associated with diversity across real-world data sources (RWDS) repurposed for secondary use in pharmacoepidemiologic studies. Our aims were to identify, describe and characterize practices, recommendations and tools for collecting and reporting diversity across RWDSs, and explore how leveraging diversity could improve the quality of evidence. METHODS: In a preliminary phase, keywords for a literature search and selection tool were designed using a set of documents considered to be key by the coauthors. Next, a systematic search was conducted up to December 2021. The resulting documents were screened based on titles and abstracts, then based on full texts using the selection tool. Selected documents were reviewed to extract information on topics related to collecting and reporting RWDS diversity. A content analysis of the topics identified explicit and latent themes. RESULTS: Across the 91 selected documents, 12 topics were identified: 9 dimensions used to describe RWDS (organization accessing the data source, data originator, prompt, inclusion of population, content, data dictionary, time span, healthcare system and culture, and data quality), tools to summarize such dimensions, challenges, and opportunities arising from diversity. Thirty-six themes were identified within the dimensions. Opportunities arising from data diversity included multiple imputation and standardization. CONCLUSIONS: The dimensions identified across a large number of publications lay the foundation for formal guidance on reporting diversity of data sources to facilitate interpretation and enhance replicability and validity of RWE.

A comparison of four self-controlled study designs in an analysis of COVID-19 vaccines and myocarditis using five European databases.

INTRODUCTION: The aim of this study was to assess the possible extent of bias due to violation of a core assumption (event-dependent exposures) when using self-controlled designs to analyse the association between COVID-19 vaccines and myocarditis. METHODS: We used data from five European databases (Spain: BIFAP, FISABIO VID, and SIDIAP; Italy: ARS-Tuscany; England: CPRD Aurum) converted to the ConcePTION Common Data Model. Individuals who experienced both myocarditis and were vaccinated against COVID-19 between 1 September 2020 and the end of data availability in each country were included. We compared a self-controlled risk interval study (SCRI) using a pre-vaccination control window, an SCRI using a post-vaccination control window, a standard SCCS and an extension of the SCCS designed to handle violations of the assumption of event-dependent exposures. RESULTS: We included 1,757 cases of myocarditis. For analyses of the first dose of the Pfizer vaccine, to which all databases contributed information, we found results consistent with a null effect in both of the SCRI and extended SCCS, but some indication of a harmful effect in a standard SCCS. For the second dose, we found evidence of a harmful association for all study designs, with relatively similar effect sizes (SCRI pre = 1.99, 1.40 - 2.82; SCRI post 2.13, 95 %CI - 1.43, 3.18; standard SCCS 1.79, 95 %CI 1.31 - 2.44, extended SCCS 1.52, 95 %CI = 1.08 - 2.15). Adjustment for calendar time did not change these conclusions. Findings using all designs were also consistent with a harmful effect following a second dose of the Moderna vaccine. CONCLUSIONS: In the context of the known association between COVID-19 vaccines and myocarditis, we have demonstrated that two forms of SCRI and two forms of SCCS led to largely comparable results, possibly because of limited violation of the assumption of event-dependent exposures.

Sugar transporters spatially organize microbiota colonization along the longitudinal root axis of Arabidopsis.

Plant roots are functionally heterogeneous in cellular architecture, transcriptome profile, metabolic state, and microbial immunity. We hypothesized that axial differentiation may also impact spatial colonization by root microbiota along the root axis. We developed two growth systems, ArtSoil and CD-Rhizotron, to grow and then dissect Arabidopsis thaliana roots into three segments. We demonstrate that distinct endospheric and rhizosphere bacterial communities colonize the segments, supporting the hypothesis of microbiota differentiation along the axis. Root metabolite profiling of each segment reveals differential metabolite enrichment and specificity. Bioinformatic analyses and GUS histochemistry indicate microbe-induced accumulation of SWEET2, 4, and 12 sugar uniporters. Profiling of root segments from sweet mutants shows altered spatial metabolic profiles and reorganization of endospheric root microbiota. This work reveals the interdependency between root metabolites and microbial colonization and the contribution of SWEETs to spatial diversity and stability of microbial ecosystem.

Expanding the Toolbox for Genetic Manipulation in Pseudogymnoascus: RNAi-Mediated Silencing and CRISPR/Cas9-Mediated Disruption of a Polyketide Synthase Gene Involved in Red Pigment Production in P. verrucosus.

Fungi belonging to the genus Pseudogymnoascus have garnered increasing attention in recent years. One of the members of the genus, P. destructans, has been identified as the causal agent of a severe bat disease. Simultaneously, the knowledge of Pseudogymnoascus species has expanded, in parallel with the increased availability of genome sequences. Moreover, Pseudogymnoascus exhibits great potential as a producer of specialized metabolites, displaying a diverse array of biological activities. Despite these significant advancements, the genetic landscape of Pseudogymnoascus remains largely unexplored due to the scarcity of suitable molecular tools for genetic manipulation. In this study, we successfully implemented RNAi-mediated gene silencing and CRISPR/Cas9-mediated disruption in Pseudogymnoascus, using an Antarctic strain of Pseudogymnoascus verrucosus as a model. Both methods were applied to target azpA, a gene involved in red pigment biosynthesis. Silencing of the azpA gene to levels of 90% or higher eliminated red pigment production, resulting in transformants exhibiting a white phenotype. On the other hand, the CRISPR/Cas9 system led to a high percentage (73%) of transformants with a one-nucleotide insertion, thereby inactivating azpA and abolishing red pigment production, resulting in a white phenotype. The successful application of RNAi-mediated gene silencing and CRISPR/Cas9-mediated disruption represents a significant advancement in Pseudogymnoascus research, opening avenues for comprehensive functional genetic investigations within this underexplored fungal genus.

Congenital Cytomegalovirus Testing Outcomes From the ValEAR Trial.

OBJECTIVE: To determine the positivity rate of congenital cytomegalovirus (cCMV) testing among universal, hearing-targeted CMV testing (HT-cCMV) and delayed targeted dried blood spot (DBS) testing newborn screening programs, and to examine the characteristics of successful HT-cCMV testing programs. STUDY DESIGN: Prospective survey of birth hospitals performing early CMV testing. SETTING: Multiple institutions. METHODS: Birth hospitals participating in the National Institutes of Health ValEAR clinical trial were surveyed to determine the rates of cCMV positivity associated with 3 different testing approaches: universal testing, HT-cCMV, and DBS testing. A mixed methods model was created to determine associations between successful HT-cCMV screening and specific screening protocols. RESULTS: Eighty-two birth hospitals were surveyed from February 2019 to December 2021. Seven thousand six hundred seventy infants underwent universal screening, 9017 infants HT-cCMV and 535 infants delayed DBS testing. The rates of cCMV positivity were 0.5%, 1.5%, and 7.3%, respectively. The positivity rate for universal CMV screening was less during the COVID-19 pandemic than that reported prior to the pandemic. There were no statistically significant drops in positivity for any approach during the pandemic. For HT-cCMV testing, unique order sets and rigorous posttesting protocols were associated with successful screening programs. CONCLUSION: Rates of cCMV positivity differed among the 3 approaches. The rates are comparable to cohort studies reported in the literature. Universal CMV prevalence decreased during the pandemic but not significantly. Institutions with specific order set for CMV testing where the primary care physician orders the test and the nurse facilitates the testing process exhibited higher rates of HT-cCMV testing.

Community-Engaged Research (CEnR) to Address Gaps in Chronic Kidney Disease Education among Underserved Latines-The CARE Study.

Ensuring equitable chronic kidney disease (CKD) education for Latine patients with low health literacy and low English proficiency stands as a critical challenge, and the "Caridad Awareness and Education" (CARE) initiative represents our ongoing effort to address this imperative issue. In collaboration with twenty-three patients living with CKD, diabetes and/or hypertension and twelve trained Community Health Workers (CHWs) from diverse Latine subgroups, we conducted a research initiative funded by the National Kidney Foundation. Our primary objective was to co-design and test culturally tailored patient education materials (PEMs) for underserved Latine adults at risk for or diagnosed with CKD. We effectively integrated Community-Engaged Research (CEnR) principles with a Human-Centered Design (HCD) approach to create a range of CKD-PEM prototypes in Spanish. Patient preferences for printed educational materials were clear. They favored printed materials that incorporated visual content with concise text over digital, email, texts, or online resources and personalized phone outreach and the involvement of CHWs. Additionally, patients identified their unwavering commitment to their families as a forceful motivator for caring for their kidney health. Currently, a culturally and linguistically tailored CKD flipchart for one-on-one education, led by CHWs, is undergoing a pilot testing phase involving a sample of one hundred Latine patients at risk for or diagnosed with CKD. This innovative approach signifies a commitment to amplifying the insights and expertise of the Latine community afflicted by kidney health disparities, effectively embracing a CEnR to forge meaningful and impactful CKD-PEMs.

PrlaeA Affects the Production of Roquefortine C, Mycophenolic Acid, and Andrastin A in Penicillium roqueforti, but It Has Little Impact on Asexual Development.

The regulation of fungal specialized metabolism is a complex process involving various regulators. Among these regulators, LaeA, a methyltransferase protein originally discovered in Aspergillus spp., plays a crucial role. Although the role of LaeA in specialized metabolism has been studied in different fungi, its function in Penicillium roqueforti remains unknown. In this study, we employed CRISPR-Cas9 technology to disrupt the laeA gene in P. roqueforti (PrlaeA) aiming to investigate its impact on the production of the specialized metabolites roquefortine C, mycophenolic acid, and andrastin A, as well as on asexual development, because they are processes that occur in the same temporal stages within the physiology of the fungus. Our results demonstrate a substantial reduction in the production of the three metabolites upon disruption of PrlaeA, suggesting a positive regulatory role of LaeA in their biosynthesis. These findings were further supported by qRT-PCR analysis, which revealed significant downregulation in the expression of genes associated with the biosynthetic gene clusters (BGCs) responsible for producing roquefortine C, mycophenolic acid, and andrastin A in the ΔPrlaeA strains compared with the wild-type P. roqueforti. Regarding asexual development, the disruption of PrlaeA led to a slight decrease in colony growth rate, while conidiation and conidial germination remained unaffected. Taken together, our results suggest that LaeA positively regulates the expression of the analyzed BGCs and the production of their corresponding metabolites in P. roqueforti, but it has little impact on asexual development.

CRISPR/Cas9-Mediated Disruption of the pcz1 Gene and Its Impact on Growth, Development, and Penicillin Production in Penicillium rubens.

Penicillium rubens is a filamentous fungus of great biotechnological importance due to its role as an industrial producer of the antibiotic penicillin. However, despite its significance, our understanding of the regulatory mechanisms governing biological processes in this fungus is still limited. In fungi, zinc finger proteins containing a Zn(II)2Cys6 domain are particularly interesting regulators. Although the P. rubens genome harbors many genes encoding proteins with this domain, only two of them have been investigated thus far. In this study, we employed CRISPR-Cas9 technology to disrupt the pcz1 gene, which encodes a Zn(II)2Cys6 protein in P. rubens. The disruption of pcz1 resulted in a decrease in the production of penicillin in P. rubens. This decrease in penicillin production was accompanied by the downregulation of the expression of pcbAB, pcbC and penDE genes, which form the biosynthetic gene cluster responsible for penicillin production. Moreover, the disruption of pcz1 also impacts on asexual development, leading to decreased growth and conidiation, as well as enhanced conidial germination. Collectively, our results indicate that pcz1 acts as a positive regulator of penicillin production, growth, and conidiation, while functioning as a negative regulator of conidial germination in P. rubens. To the best of our knowledge, this is the first report involving a gene encoding a Zn(II)2Cys6 protein in the regulation of penicillin biosynthesis in P. rubens.

APOL1 Gene Variants and Risk for Cardiovascular Disease.

INTRODUCTION: The association of APOL1 risk variants with cardiovascular risk and cardiovascular disease (CVD) in observational and clinical trials has had inconsistent results. We aim to assess the relationship between the presence of APOL1 risk variants and the CVD risk in Afro-descendant patients with end-stage renal disease (ESRD). METHODS: We performed an observational, cross-sectional study of Afro-descendant adult patients with ESRD who were on the waitlist for a kidney transplant. Associations of APOL1 genotypes (high-risk [HR] = 2 alleles; low-risk [LR] = 0 or 1 allele) with cardiovascular risk were the primary clinical endpoint. The relation was evaluated using univariate and multivariate analysis. RESULTS: We enrolled a total of 102 patients with ESRD; 37% (38 patients) had APOL1 HR status with two alleles in homozygous (G1/G1 = 21 and G2/G2 = 3) or compound heterozygote (G1/G2 = 14) form and 63% (64 patients) had APOL1 LR status. No significant association was found between HR APOL1 genotypes and high cardiovascular risk (in adjusted Colombia Framingham Risk Score). APOL1 HR versus LR variants were not independently associated with left ventricular hypertrophy or systolic dysfunction. No cardiovascular deaths occurred during the follow-up. CONCLUSION: In Afro-descendent patients with ESRD, APOL1 HR status is not associated with the increase in cardiovascular risk profile and metabolic disturbances.

Distancia de la raíz a las tablas óseas y piso nasal de dientes anteriores maxilares con indicación de microcirugía apical / Root to bone table and nasal floor distance of maxillary anterior teeth with indication for apical microsurgery / Tabela raiz-osso e distância do pavimento nasal dos dentes anteriores superiores com indicação para microcirurgia apical

RESUMEN Objetivo: Evaluar la distancia de la raíz a las tablas óseas y piso nasal de dientes anteriores maxilares con indicación de microcirugía apical. Material y métodos: La muestra fue de 44 imágenes tomográficas computarizadas de haz cónico previas al procedimiento de microcirugía apical; además, se seleccionaron 31 imágenes para la comparación con los dientes contralaterales sin indicación de microcirugía apical. Se midió la distancia de la raíz a las tablas óseas y al piso nasal. Resultados: La distancia de la superficie radicular a las tablas óseas vestibular y palatina a 3 mm del ápice fue de 0,98 ± 0,67 mm y 4,26 ± 2,97 mm para el incisivo central; 0,77 ± 0,50 mm y 2,12 ± 1,22 mm para el incisivo lateral; y 0,52 ± 0,63 mm y 5,31 ± 1,38 mm para el canino, respectivamente. La distancia más corta del ápice al piso nasal fue de 9,56 ± 2,88 mm para el incisivo central; 10,33 ± 2,97 mm para el incisivo lateral; y 5,73 ± 2,57 mm para el canino. Solo se encontró una distancia mayor, estadísticamente significativa, del ápice al piso nasal del incisivo lateral con indicación de microcirugía apical en comparación con el incisivo lateral sin indicación de microcirugía apical. Conclusiones: La distancia de la raíz a la tabla ósea vestibular es menor que la distancia de la misma a la tabla ósea palatina. El ápice más próximo al piso nasal fue del canino. Los dientes anteriores maxilares con y sin indicación de microcirugía apical mostraron distancias similares de la raíz a las tablas óseas y piso nasal.

ABSTRACT Objective: To evaluate the distance from the root to the bone tables and nasal floor of maxillary anterior teeth with indication for apical microsurgery. Material and methods : The sample consisted of 44 cone beam computed tomographic images prior to the apical microsurgery procedure; in addition, 31 images were selected for comparison with contralateral teeth without indication for apical microsurgery. The distance from the root to the bone tables and nasal floor was measured. Results: The distance from the root surface to the vestibular and palatal bone tables 3 mm from the apex was 0.98 ± 0.67 mm and 4.26 ± 2.97 mm for the central incisor; 0.77 ± 0.50 mm and 2.12 ± 1.22 mm for the lateral incisor; and 0.52 ± 0.63 mm and 5.31 ± 1.38 mm for the canine, respectively. The shortest distance from the apex to the nasal floor was 9.56 ± 2.88 mm for the central incisor, 10.33 ± 2.97 mm for the lateral incisor, and 5.73 ± 2.57 mm for the canine. A statistically significant greater distance from the apex to the nasal floor was found only for the lateral incisor with indication for apical microsurgery compared to the lateral incisor without indication for apical microsurgery. Conclusions: The distance from the root to the vestibular bone table is less than from the root to the palatal bone table. The apex closest to the nasal floor was that of the canine. Maxillary anterior teeth with and without indication for apical microsurgery showed similar distances from the root to the bone tables and nasal floor.

RESUMO Objetivo: avaliar a distância da raiz às tábuas ósseas e ao assoalho nasal de dentes anteriores superiores com indicação de microcirurgia apical. Material e métodos: a amostra foi composta por 44 imagens de tomografia computadorizada de feixe cônico antes do procedimento de microcirurgia apical; além disso, 31 imagens foram selecionadas para comparação com dentes contralaterais sem indicação de microcirurgia apical. Foi medida a distância da raiz até as tábuas ósseas e o assoalho nasal. Resultados: a distância da superfície radicular às tábuas ósseas vestibular e palatina, a 3mm do ápice, foi de 0,98mm ± 0,67mm e 4,26mm ± 2,97mm para o incisivo central; 0,77mm ± 0,50mm e 2,12mm ± 1,22mm para o incisivo lateral; e 0,52mm ± 0,63mm e 5,31mm ± 1,38mm para o canino, respetivamente. A menor distância entre o ápice e o assoalho nasal foi de 9,56 ± 2,88 mm para o incisivo central; 10,33 ± 2,97 mm para o incisivo lateral; e 5,73 ± 2,57 mm para o canino. Uma distância estatisticamente significativa maior do ápice ao assoalho nasal foi encontrada apenas para o incisivo lateral com indicação de microcirurgia apical em comparação com o incisivo lateral sem indicação de microcirurgia apical. Conclusões: a distância da raiz até a tábua óssea vestibular é menor do que a distância da raiz até a tábua óssea palatina. O ápice mais próximo do assoalho nasal foi o do canino. Os dentes anteriores superiores com e sem indicação de microcirurgia apical apresentaram distâncias semelhantes da raiz às tábuas ósseas e ao assoalho nasal.

Impact of the 2018 revised Pregnancy Prevention Programme by the European Medicines Agency on the use of oral retinoids in females of childbearing age in Denmark, Italy, Netherlands, and Spain: an interrupted time series analysis.

Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.

COVID-19 Vaccine Safety Monitoring Studies in Low- and Middle-Income Countries (LMICs)-A Systematic Review of Study Designs and Methods.

BACKGROUND: Post-marketing vaccine safety surveillance aims to monitor and quantify adverse events following immunization in a population, but little is known about their implementation in low- and middle-income countries (LMICs). We aimed to synthesize methodological approaches used to assess adverse events following COVID-19 vaccination in LMICs. METHODS: For this systematic review, we searched articles published from 1 December 2019 to 18 February 2022 in main databases, including MEDLINE and Embase. We included all peer-reviewed observational COVID-19 vaccine safety monitoring studies. We excluded randomized controlled trials and case reports. We extracted data using a standardized extraction form. Two authors assessed study quality using the modified Newcastle-Ottawa Quality Assessment Scale. All findings were summarized narratively using frequency tables and figures. RESULTS: Our search found 4254 studies, of which 58 were eligible for analysis. Many of the studies included in this review were conducted in middle-income countries, with 26 studies (45%) in lower-middle-income and 28 (48%) in upper-middle-income countries. More specifically, 14 studies were conducted in the Middle East region, 16 in South Asia, 8 in Latin America, 8 in Europe and Central Asia, and 4 in Africa. Only 3% scored 7-8 points (good quality) on the Newcastle-Ottawa Scale methodological quality assessment, while 10% got 5-6 points (medium). About 15 studies (25.9%) used a cohort study design and the rest were cross-sectional. In half of them (50%), vaccination data were gathered from the participants' self-reporting methods. Seventeen studies (29.3%) used multivariable binary logistic regression and three (5.2%) used survival analyses. Only 12 studies (20.7%) performed model diagnostics and validity checks (e.g., the goodness of fit, identification of outliers, and co-linearity). CONCLUSIONS: Published studies on COVID-19 vaccine safety surveillance in LMICs are limited in number and the methods used do not often address potential confounders. Active surveillance of vaccines in LMICs are needed to advocate vaccination programs. Implementing training programs in pharmacoepidemiology in LMICs is essential.

Impact of 2018 EU Risk Minimisation Measures and Revised Pregnancy Prevention Programme on Utilisation and Prescribing Trends of Medicinal Products Containing Valproate: An Interrupted Time Series Study.

INTRODUCTION: Due to established teratogenicity of valproates, the EU risk minimisation measures (RMMs) with a pregnancy prevention programme (PPP) for valproate were updated in March 2018. OBJECTIVES: To investigate the effectiveness of the 2018 EU RMMs on valproate utilisation in five European countries/regions. METHODS: A multi-database, times series study of females of childbearing potential (12-55 years) was conducted using electronic medical records from five countries/regions (01.01.2010-31.12.2020): Denmark, Tuscany (Italy), Spain, the Netherlands, and the UK. Clinical and demographic information from each database was transformed to the ConcePTION Common Data Model, quality checks were conducted and a distributed analysis was performed using common scripts. Incident and prevalent use of valproate, proportion of discontinuers and switchers to alternative medicine, frequency of contraception coverage during valproate use, and occurrence of pregnancies during valproate exposure were estimated per month. Interrupted time series analyses were conducted to estimate the level or trend change in the outcome measures. RESULTS: We included 69,533 valproate users from 9,699,371 females of childbearing potential from the five participating centres. A significant decline in prevalent use of valproates was observed in Tuscany, Italy (mean difference post-intervention -7.7%), Spain (-11.3%), and UK (-5.9%) and a non-significant decline in the Netherlands (-3.3%), but no decline in incident use after the 2018 RMMs compared to the period before. The monthly proportion of compliant valproate prescriptions/dispensings with a contraceptive coverage was low (<25%), with an increase after the 2018 RMMs only in the Netherlands (mean difference post-intervention 12%). There was no significant increase in switching rates from valproates to alternative medicine after the 2018 intervention in any of the countries/regions. We observed a substantial number of concurrent pregnancies during valproate exposure, but with a declining rate after the 2018 RMMs in Tuscany, Italy (0.70 per 1000 valproate users pre- and 0.27 post-intervention), Spain (0.48 and 0.13), the Netherlands (0.34 and 0.00), and an increasing rate in UK (1.13 and 5.07). CONCLUSION: There was a small impact of the 2018 RMMs on valproate use in the studied European countries/regions. The substantial number of concurrent pregnancies with valproate exposure warrants a careful monitoring of implementation of the existing PPP for valproate in clinical practice in Europe, to see if there is any need for additional measures in the future.

Intention to Migrate Due to COVID-19: a Study for El Salvador.

Economic and social conditions have deteriorated worldwide during the COVID-19 pandemic. Migration theory and international organizations indicate that these increasingly fragile social conditions represent powerful incentives to migrate. Normally, studies addressing international migration and COVID-19 focus on transit and destination countries, with substantially less literature centered on origin nations. Trying to close that gap, the present article aims to identify and quantify economic determinants that explain the intention of Salvadorians to migrate abroad. Using a probabilistic sample and a logistic model, a number of renowned economic variables for migration studies were used to investigate Salvadorian's intention to emigrate. Results demonstrated a stark reduction in migration intentions in 2020. Moreover, the risk of losing one's job is by far the most prominent factor explaining the intention to migrate. Other aspects, such as employment and salaries, also showed statistically significant values. Additionally, results report women being less likely to migrate and age to have a negligible effect. The text concludes by indicating some public initiatives that could be implemented to support people who choose to act upon their intentions and embark on emigration.

Domestic work and migration in the United States: a characterization of Honduran women / Trabalho doméstico e migração nos Estados Unidos: uma caracterização de mulheres hondurenhas / Trabajo doméstico y migración en los Estados Unidos: una caracterización de mujeres hondureñas

Abstract Given the lack of studies focused on Honduran domestic workers abroad, this article aims to characterize Honduran women living in the U.S. employed in domestic occupations. For this purpose, I employed survey data on women living in five American states, and calculated descriptive and inferential statistics. Furthermore, I employed binary logistic regression modeling to analyze the determinants of domestic work participation. When compared with all other occupations, domestic female workers of Honduran origin present significant differences in age, number of dependents, asset ownership, savings, income, and bank account ownership. Similarly, age (95% CI 0.92-2.63, p = 0.94), savings (95% CI 0.01-0.97, p = 0.047), account ownership in Honduras (95% CI 0.88-71.05, p = 0.064), monthly income (95% CI 0.99-1.00, p = 0.096), and social security (95% CI 0.02-1.29, p = 0.086) seem to be the key determinants explaining domestic work participation. Engaging and promoting compliance with international legal instruments might provide a means to consolidate the rights of these populations. The article concludes by highlighting future lines of research regarding the migration and rights of Honduras and Central American women living in the U.S.

Resumo Em função da escassa literatura sobre o tema, o presente artigo visa caracterizar as mulheres hondurenhas empregadas em ocupações domésticas nos Estados Unidos. Com esse objetivo, empregam-se questionários preenchidos por mulheres morando em cinco estados desse país norte-americano. Para realizar tal caracterização, é utilizada estatística descritiva e inferencial. Adicionalmente, emprega-se regressão logística para analisar os determinantes da participação em empregos domésticos. Quando comparadas com todas as outras ocupações, as mulheres hondurenhas fazendo trabalhos domésticos possuem diferenças em termos de idade, número de dependentes, posse de bens, poupanças e existência de conta bancária. Similarmente, a análise dos determinantes estatísticos mostra que variáveis significativas incluem idade (95% IC 0,92-2,63 p = 0.94), poupanças (95% IC 0,01-0,97, p = 0.047), existência de conta bancária (95% IC 0,88-71,05, p = 0.064), renda mensal (95% IC 0,99-1.00, p = 0.096) e contribuição à previdência social (95% IC 0,02-1,29 p = 0.086). Promover a adoção de instrumentos de direito internacional pode representar uma alternativa para fomentar os direitos humanos desse grupo de pessoas. O artigo finaliza ressaltando possíveis linhas de pesquisa relacionadas à migração de mulheres hondurenhas e da América Central morando nos Estados Unidos.

Resumen En vista de la escasa literatura centrada en trabajadoras domésticas hondureñas en el extranjero, el presente artículo busca caracterizar a mujeres hondureñas empleadas en ocupaciones domésticas en Estados Unidos. Para ello, se utilizan encuestas aplicadas a mujeres hondureñas que viven en cinco estados del país norteamericano y se emplea estadística descriptiva e inferencial. Adicionalmente, se usa una regresión logística para analizar los determinantes de la participación en empleos domésticos. Cuando se compara con todas las otras ocupaciones, las mujeres hondureñas que trabajan en este rubro presentan diferencias en edad, número de dependientes, posesión de bienes, ahorros y posesión de cuenta bancaria. Similarmente, el análisis de determinantes muestra las variables significativas que incluyen edad (95 % IC 0,92-2,63 p= 0,94), ahorros (95 % IC 0,01-0,97, p= 0,047), cuenta bancaria (95 % IC 0,88-71,05, p= 0,064), ingreso mensual (95 % IC 0,99-1,00, p= 0,096) y seguro social (95 % IC 0,02-1,29 p= 0,086). Promover la adopción de instrumentos de derecho internacional puede ser una alternativa para fomentar los derechos humanos de esta población. El artículo termina mostrando líneas de investigación sobre migración para mujeres hondureñas y centroamericanas viviendo en Estados Unidos.

Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries.

Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39-49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed.

Effects of the COVID-19 pandemic on food insecurity in El Salvador during 2020.

Objective: This study sought to quantify the prevalence of food insecurity among Salvadorian households, to identify the determinants of food insecurity and to explore the impact of the COVID-19 pandemic on food insecurity. Methods: A nationwide, representative random sample of 2358 households was used for this cross-sectional study. The Household Hunger Scale (HHS) was used to assess the prevalence of food insecurity during a 30-day period. For comparison, three items were used from the Household Food Insecurity Experience Scale (HFIES), which measures hunger occurring during a 12-month time frame. For determinant analysis, binary logistic regression was used for the HHS and ordered logistic regression for the HFIES. Results: The prevalence of food insecurity was 6.45% (152/2356) among Salvadorian households when the HHS was used, affecting 5.48% (129/2356) to a moderate degree and 0.98% (23/2356) to a severe degree. The prevalence significantly increased when the HFIES scale items were used, with 35.41% (835/2358) of households being affected, a figure closer to the national poverty level. Determinants of food insecurity according to the HHS included agricultural problems (P = 0.00, odds ratio [OR] =1.69), the household's prepandemic income (P = 0.00, OR = 0.48) and higher educational levels (i.e. having a secondary education [P = 0.00, OR = 0.31], technical [P = 0.03, OR = 0.24] or university education [P = 0.00, OR = 0.05]). When using the HFIES, the determinants were similar (i.e. income, agricultural problems, educational level). In more than 94% (744/785) of households, participants reported that food insecurity was exacerbated by the COVID-19 pandemic. Conclusions: When compared with other relevant international studies, the prevalence of food insecurity identified using the HHS - only 6.45% - was low for El Salvador. However, when using the HFIES scale, the prevalence rose to 35.41% of households. Some determinants align with previous studies, namely income, educational level and agricultural problems. The COVID-19 pandemic appeared to have direct effects on food insecurity.

Effects of the COVID-19 pandemic on food insecurity in El Salvador during 2020

[ABSTRACT]. bjective. This study sought to quantify the prevalence of food insecurity among Salvadorian households, to identify the determinants of food insecurity and to explore the impact of the COVID-19 pandemic on food insecurity. Methods. A nationwide, representative random sample of 2358 households was used for this cross-sectional study. The Household Hunger Scale (HHS) was used to assess the prevalence of food insecurity during a 30-day period. For comparison, three items were used from the Household Food Insecurity Experience Scale (HFIES), which measures hunger occurring during a 12-month time frame. For determinant analysis, binary logistic regression was used for the HHS and ordered logistic regression for the HFIES. Results. The prevalence of food insecurity was 6.45% (152/2356) among Salvadorian households when the HHS was used, affecting 5.48% (129/2356) to a moderate degree and 0.98% (23/2356) to a severe degree. The prevalence significantly increased when the HFIES scale items were used, with 35.41% (835/2358) of house- holds being affected, a figure closer to the national poverty level. Determinants of food insecurity according to the HHS included agricultural problems (P = 0.00, odds ratio [OR] =1.69), the household’s prepandemic income (P = 0.00, OR = 0.48) and higher educational levels (i.e. having a secondary education [P = 0.00, OR = 0.31], technical [P = 0.03, OR = 0.24] or university education [P = 0.00, OR = 0.05]). When using the HFIES, the determinants were similar (i.e. income, agricultural problems, educational level). In more than 94% (744/785) of households, participants reported that food insecurity was exacerbated by the COVID-19 pandemic. Conclusions. When compared with other relevant international studies, the prevalence of food insecurity identified using the HHS – only 6.45% – was low for El Salvador. However, when using the HFIES scale, the prevalence rose to 35.41% of households. Some determinants align with previous studies, namely income, educational level and agricultural problems. The COVID-19 pandemic appeared to have direct effects on food insecurity

[RESUMEN]. Objetivo. Este estudio tuvo por objetivo cuantificar la prevalencia de la inseguridad alimentaria en los hogares salvadoreños, determinar cuáles son los determinantes de la inseguridad alimentaria y explorar los efectos de la pandemia de COVID-19 en la inseguridad alimentaria. Métodos. En este estudio transversal se utilizó una muestra aleatoria representativa a nivel nacional de 2 358 hogares. Se empleó la escala del hambre en el hogar (HHS, por su sigla en inglés) para evaluar la prevalencia de la inseguridad alimentaria en un período de 30 días. Para la comparación, se utilizaron tres indicadores de la escala de experiencia de inseguridad alimentaria en el hogar (HFIES, por su sigla en inglés), que mide el hambre durante un período de 12 meses. Para el análisis de los determinantes, se empleó la regresión logística binaria para HHS y la regresión logística ordenada para HFIES. Resultados. La prevalencia de la inseguridad alimentaria fue de 6,45% (152/2356) en los hogares salvador- eños al emplearse HHS, y afectó moderadamente a 5,48% (129/2356) y gravemente a 0,98% (23/2356). La prevalencia aumentó de forma considerable al utilizarse los indicadores de HFIES, con 35,41% (835/2358) de los hogares afectados, una cifra más cercana al nivel nacional de pobreza. Los determinantes de la inseguri- dad alimentaria según HHS incluyeron problemas agrícolas (P = 0,00, razón de posibilidades [OR] = 1,69), los ingresos familiares previos a la pandemia (P = 0,00, OR = 0,48) y niveles educativos superiores (educación secundaria [P = 0,00, OR = 0,31], formación técnica [P = 0,03, OR = 0,24] o universitaria [P = 0,00, OR = 0,05]). Con HFIES, los determinantes fueron similares (ingresos, problemas agrícolas, nivel educativo). En más de 94% (744/785) de los hogares, los participantes notificaron que la inseguridad alimentaria se agravó por la pandemia de COVID-19. Conclusiones. En comparación con otros estudios internacionales pertinentes, la prevalencia de la insegu- ridad alimentaria mediante HHS –de solo 6,45%– fue baja en El Salvador. Sin embargo, al utilizar HFIES, la prevalencia aumentó a 35,41% de los hogares. Algunos determinantes coinciden con estudios anteriores, como los ingresos, el nivel educativo y los problemas agrícolas. La pandemia de COVID-19 parece tener un impacto directo en la inseguridad alimentaria.

[RESUMO]. Objetivo. Este estudo procurou quantificar a prevalência de insegurança alimentar entre as famílias salvador- enhas, identificar os determinantes de insegurança alimentar e explorar o impacto da pandemia de COVID-19 sobre a insegurança alimentar. Métodos. Este estudo transversal foi realizado com uma amostra representativa nacional randomizada de 2358 domicílios. Usou-se a Household Hunger Scale (HHS) [escala de fome domiciliar] para avaliar a prevalência de insegurança alimentar durante um período de 30 dias. Para fins de comparação, usaram-se três itens da Household Food Insecurity Experience Scale (HFIES) [escala de experiência de insegurança alimentar domiciliar], que mede a fome durante um período de 12 meses. Para a análise de determinantes, usou-se a regressão logística binária com a HHS e a regressão logística ordenada com a HFIES. Resultados. A prevalência de insegurança alimentar nos domicílios salvadorenhos medida com a HHS foi de 6,45% (152/2356), sendo moderada em 5,48% (129/2356) e grave em 0,98% (23/2356). Quando se usaram os itens da HFIES, a prevalência aumentou consideravelmente, com 35,41% (835/2358) dos domicílios afetados – um número mais próximo do nível nacional de pobreza. Entre os determinantes da insegurança alimentar, de acordo com a HHS, estavam os problemas agrícolas (P = 0,00, razão de chances [RC] = 1,69), a renda familiar pré-pandemia (P = 0,00, RC = 0,48) e a maior escolaridade (ou seja, educação secundária [P = 0,00, RC = 0,31], técnica [P = 0,03, RC = 0,24] ou universitária [P = 0,00, RC = 0,05]). Com a HFIES, os determinantes foram semelhantes (ou seja, renda, problemas agrícolas e escolaridade). Em mais de 94% (744/785) dos domicílios, os participantes relataram exacerbação da insegurança alimentar pela pandemia de COVID-19. Conclusões. Em comparação com outros estudos internacionais pertinentes, a prevalência de insegurança alimentar identificada com uso da HHS – somente 6,45% – foi baixa em El Salvador. Entretanto, quando se usou a HFIES, a prevalência aumentou para 35,41% dos domicílios. Alguns determinantes coincidem com os de estudos anteriores, a saber, renda, escolaridade e problemas agrícolas. Aparentemente, a pandemia de COVID-19 teve efeitos diretos sobre a insegurança alimentar.